ctDNA-guided adjuvant treatment after radical-intent treatment of metastatic spread from colorectal cancer-the first interim results from the OPTIMISE study.

Autor: Callesen LB; Department of Oncology, Aarhus University Hospital, Aarhus, Denmark., Hansen TF; Department of Oncology, Vejle Hospital, University Hospital of Southern Denmark, Vejle, Denmark., Andersen RF; Department of Biochemistry and Immunology, Vejle Hospital, University Hospital of Southern Denmark, Vejle, Denmark., Pallisgaard N; Department of Pathology, Zealand University Hospital, Næstved, Denmark., Kramer S; Department of Nuclear Medicine & PET-Centre, Aarhus University Hospital, Aarhus, Denmark., Schlander S; Department of Radiology, Aarhus University Hospital, Aarhus, Denmark., Rafaelsen SR; Department of Radiology, Vejle Hospital, University Hospital of Southern Denmark, Vejle, Denmark., Boysen AK; Department of Oncology, Aarhus University Hospital, Aarhus, Denmark., Jensen LH; Department of Oncology, Vejle Hospital, University Hospital of Southern Denmark, Vejle, Denmark., Jakobsen A; Department of Oncology, Vejle Hospital, University Hospital of Southern Denmark, Vejle, Denmark., Spindler KG; Department of Oncology, Aarhus University Hospital, Aarhus, Denmark.
Jazyk: angličtina
Zdroj: Acta oncologica (Stockholm, Sweden) [Acta Oncol] 2023 Dec; Vol. 62 (12), pp. 1742-1748. Date of Electronic Publication: 2023 Nov 25.
DOI: 10.1080/0284186X.2023.2259083
Abstrakt: Background: Patients with detectable ctDNA after radical-intent treatment of metastatic spread from colorectal cancer (mCRC) have a very high risk of recurrence, which may be prevented with intensified adjuvant chemotherapy (aCTh). In the OPTIMISE study, we investigate ctDNA-guided aCTh after radical-intent treatment of mCRC. Here we present results from the preplanned interim analysis.
Material and Methods: The study is an open-label 1:1 randomized clinical trial comparing ctDNA-guided aCTh against standard of care (SOC), with a run-in phase investigating feasibility measures. Key inclusion criteria; radical-intent treatment for mCRC and clinically eligible for triple-agent chemotherapy. Patients underwent a PET-CT scan before randomization. ctDNA analyses of plasma samples were done by ddPCR, detecting CRC-specific mutations and methylation of the NPY gene. In the ctDNA-guided arm, ctDNA positivity led to an escalation strategy with triple-agent chemotherapy, and conversely ctDNA negativity led to a de-escalation strategy by shared-decision making. Patients randomized to the standard arm were treated according to SOC. Feasibility measures for the run-in phase were; the inclusion of 30 patients over 12 months in two Danish hospitals, compliance with randomization >80%, rate of PET-CT-positive findings <20%, and eligibility for triple-agent chemotherapy >80%.
Results: Thirty-two patients were included. The rate of PET-CT-positive cases was 22% ( n  = 7/32). Ninety-seven percent of the patients were randomized. Fourteen patients were randomly assigned to SOC and sixteen to ctDNA-guided adjuvant treatment and follow-up. All analyses of baseline plasma samples in the ctDNA-guided arm passed the quality control, and 19% were ctDNA positive. The median time to result was three working days. All ctDNA-positive patients were eligible for triple-agent chemotherapy.
Conclusion: The study was proven to be feasible and continues in the planned large-scale phase II trial. Results from the OPTIMISE study will potentially optimize the adjuvant treatment of patients undergoing radical-intent treatment of mCRC, thereby improving survival and reducing chemotherapy-related toxicity.
Databáze: MEDLINE
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